Gadolinium-Doped BTO-Functionalized Nanocomposites with Enhanced MRI and X-ray Dual Imaging to Simulate the Electrical Properties of Bone.

Physicochemical properties of biomaterials play a regulatory role in osteoblast proliferation and differentiation. Inspired by the electrical properties of natural bone, the electroactive composites applied to osteogenesis have gradually become the hotspot of research. In this work, an electroactive biocomposite of poly(lactic-co-glycolic acid) mixed with gadolinium-doped barium titanate nanoparticles (Gd-BTO NPs) was investigated to establish the structure-activity relationship between electrical property, especially surface potential, and osteogenic activity. Furthermore, the potential mechanism was also explored. The results showed that the introduction of Gd-BTO NPs was more conducive to improve the elastic modulus and beneficial to utilize MRI and X-ray dual imaging. The electrical characteristics of composites indicate that the introduction of Gd-BTO NPs can effectively improve the electrical properties of materials including dielectricity, piezoelectricity, and surface potential. Moreover, adjusting the amount of gadolinium doping could optimize electrical activity and enhance MRI compatibility. The surface potential of 0.2Gd-BTO/PLGA could reach -58.2 to -60.9 mV at pH values from 7 to 9. Functional studies on cells revealed that the negative surface potential of poled Gd-BTO/PLGA enhanced cell attachment and osteogenic differentiation significantly. Furthermore, the negative surface potential could induce intracellular Ca2+ ion concentration oscillation and improve osteogenic differentiation via the calcineurin/NFAT signal pathway. These findings suggest that electroactive Gd-BTO/PLGA nanocomposites may have huge potential for bone regeneration and be expected to have wide applications in the field of bone tissue engineering.